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  4. Calcineurin inhibition in splenocytes induced by pavlovian conditioning
 
research article

Calcineurin inhibition in splenocytes induced by pavlovian conditioning

Pacheco-López, Gustavo
•
Riether, Carsten
•
Doenlen, Raphael
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2008
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology

Pavlovian conditioning is one of the major neurobiological mechanisms of placebo effects, potentially influencing the course of specific diseases and the response to a pharmacological therapy, such as immunosuppression. In our study with behaviorally conditioned rats, a relevant taste (0.2% saccharin) preceded the application of the immunosuppressive drug cyclosporin A (CsA), a specific calcineurin (CaN) inhibitor. Our results demonstrate that through pavlovian conditioning the particular pharmacological properties of CsA can be transferred to a neutral taste, i.e., CaN activity was inhibited in splenocytes from conditioned rats after reexposure to the gustatory stimulus. Concomitant immune consequences were observed on ex vivo mitogenic challenge (anti-CD3). Particularly, Th1-cytokine, but not Th2-cytokine, production and cell proliferation were impeded. Appropriate pharmacological and behavioral controls certify that all these changes in T-lymphocyte reactivity are attributable to mere taste reexposure. Furthermore, the underlying sympathetic-lymphocyte interaction was revealed modeling the conditioned response in vitro. CaN activity in CD4(+) T lymphocytes is reduced by beta-adrenergic stimulation (terbutaline), with these effects antagonized by the beta-adrenoreceptor antagonist nadolol. In summary, CaN was identified as the intracellular target for inducing conditioned immunosuppression by CsA, contributing to our understanding of the intracellular mechanisms behind "learned placebo effects."

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Type
research article
DOI
10.1096/fj.08-115683
Author(s)
Pacheco-López, Gustavo
Riether, Carsten
Doenlen, Raphael
Engler, Harald
Niemi, Maj-Britt
Engler, Andrea
Kavelaars, Annemieke
Heijnen, Cobi J.
Schedlowski, Manfred
Date Issued

2008

Published in
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume

23

Issue

4

Start page

1161

End page

7

Editorial or Peer reviewed

REVIEWED

Written at

OTHER

EPFL units
SV  
Available on Infoscience
January 19, 2012
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/76757
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